4.7 Review

Mitochondrial respiratory complexes: Significance in human mitochondrial disorders and cancers

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 237, Issue 11, Pages 4049-4078

Publisher

WILEY
DOI: 10.1002/jcp.30869

Keywords

ATP; cancer; genetic disorders; mitochondria; oxidative phosphorylation (OXPHOS); respiratory complexes

Funding

  1. [CA204801]
  2. [CA231925]
  3. [CA224306]

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Mitochondria play a crucial role in cellular energy production and signaling pathways, and alterations in respiratory complexes can lead to mitochondrial disorders and cancer development.
Mitochondria are pivotal organelles that govern cellular energy production through the oxidative phosphorylation system utilizing five respiratory complexes. In addition, mitochondria also contribute to various critical signaling pathways including apoptosis, damage-associated molecular patterns, calcium homeostasis, lipid, and amino acid biosynthesis. Among these diverse functions, the energy generation program oversee by mitochondria represents an immaculate orchestration and functional coordination between the mitochondria and nuclear encoded molecules. Perturbation in this program through respiratory complexes' alteration results in the manifestation of various mitochondrial disorders and malignancy, which is alarmingly becoming evident in the recent literature. Considering the clinical relevance and importance of this emerging medical problem, this review sheds light on the timing and nature of molecular alterations in various respiratory complexes and their functional consequences observed in various mitochondrial disorders and human cancers. Finally, we discussed how this wealth of information could be exploited and tailored to develop respiratory complex targeted personalized therapeutics and biomarkers for better management of various incurable human mitochondrial disorders and cancers.

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